Date Published:
2014 Jun

Publication Type:
Journal Article

Authors:

S.B. Yuan
Y. Shi
J. Chen
X. Zhou
G. Li
B.B. Gelman
J.G. Lisinicchia
S.M. Carlton
M.R. Ferguson
A. Tan
S.K. Sarna
S.J. Tang

Secondary:
Ann Neurol

Volume:
75

Pagination:
837-50

Issue:
6

PMID:
24633867

URL:
https://pubmed.ncbi.nlm.nih.gov/24633867

DOI:
10.1002/ana.24139

Keywords:
Adult;Animals;Case-Control Studies;Disease Models, Animal;External;Female;Ganglia, Spinal;HIV Envelope Protein gp120;HIV Infections;Humans;Hyperalgesia;Male;Mice;Mice, Inbred C57BL;Middle Aged;Pain;Pain Threshold;Peripheral Nervous System Diseases;Rats;Rats, Sprague-Dawley;Signal Transduction;Spinal Cord;Viral Load

Abstract:
<p>OBJECTIVE: Chronic pain is a common neurological comorbidity of human immunodeficiency virus (HIV)-1 infection, but the etiological cause remains elusive. The objective of this study was to identify the HIV-1 causal factor that critically contributes to the pathogenesis of HIV-associated pain.METHODS: We first compared the levels of HIV-1 proteins in postmortem tissues of the spinal cord dorsal horn (SDH) from HIV-1/acquired immunodeficiency syndrome patients who developed chronic pain (pain-positive HIV-1 patients) and HIV-1 patients who did not develop chronic pain (pain-negative HIV-1 patients). Then we used the HIV-1 protein that was specifically increased in the pain-positive patients to generate mouse models. Finally, we performed comparative analyses on the pathological changes in the models and the HIV-1 patients.RESULTS: We found that HIV-1 gp120 was significantly higher in pain-positive HIV-1 patients (vs pain-negative HIV-1 patients). This finding suggested that gp120 was a potential causal factor of the HIV-associated pain. To test this hypothesis, we used a mouse model generated by intrathecal injection of gp120 and compared the pathologies of the model and the pain-positive human HIV-1 patients. The results showed that the mouse model and pain-positive human HIV-1 patients developed extensive similarities in their pathological phenotypes, including pain behaviors, peripheral neuropathy, glial reactivation, synapse degeneration, and aberrant activation of pain-related signaling pathways in the SDH.INTERPRETATION: Our findings suggest that gp120 may critically contribute to the pathogenesis of HIV-associated pain.</p>